Synthesis And Antitumor Activity Of Disulfide Derivatives Based On 3-Substituted Phenyl-1,2,4-Triazole

Cancer is a serious threat to human life and health.Since most of the existing antitumor drugs have problems in terms of selectivity and side effects,it is important to design new drugs that can effectively inhibit malignant tumors.It is reported that 1,2,4-triazole derivatives have extensive biological activities,such as antitumor,anti-inflammatory,antidepressant,and antitubercular,etc.Disulfide derivatives have a variety of biological activities such as antibacterial,anti-inflammatory and antialzheimer’s disease.Especially,the antitumor potential of disulfide derivatives attracts the great interest of medicinal chemists in recent years.Based on the above biological activity characteristics,twenty-one disulfide derivatives containing 1,2,4-triazole structure were designed and synthesized in this paper,and the structures of these compounds were characterized by IR,¹H NMR,¹³C NMR and HR-ESI-MS.Using 5-FU（5-fluorouracil）and PX-12（1-methylpropyl-2-imidazolyl disulfide）as positive control drugs,the antiproliferative activity in vitro of these compounds on human lung cancer cells（A549）,human cervical cancer cells（Hela）,human liver cancer cells（SMMC-7721）and normal cells（mouse fibroblasts,L929）were determined by CCK-8 assay.The bioassay results demonstrated that most of the tested compounds exhibited antiproliferation with different degrees,and some compounds showed better effects than the two positive control drugs 5-FU and PX-12 against various cancer cell lines.For A549 cells,compounds 7c,7g and 9c exhibited highly effective antitumor activity with IC₅₀values of 3.55,3.73 and 3.94μmol/L,respectively.For Hela cells,compound 9g showed the best inhibitory effect with IC₅₀value of 3.46μmol/L.For SMMC-7721 cells,compounds 7b,7e and 8b displayed significant antiproliferative activity with IC₅₀values of 3.03,1.08 and 2.93μmol/L,respectively.Furthermore,all compounds exhibited weaker cytotoxic effects than positive controls 5-FU and PX-12on normal cell lines（L929）.These results laid a foundation for further study of the structure-activity relationship and action mechanism of these compounds.